自體免疫疾病課件

自體免疫疾病自體免疫疾病1器官特異性非器官特異性自體免疫疾病肌肉腎臟皮膚關(guān)節(jié)器官特異性非器官特異性自體免疫疾病肌肉腎臟皮膚關(guān)節(jié)2自體免疫疾病課件3自體免疫疾病課件4自體免疫疾病課件5自體免疫疾病課件6PathologicalFactorsinRheumaticDisorders

Rheumaticdiseasesaremultisystemdisorderscausedbytissuedamageresultingfromautoantibodies,cytotoxicTlymphocytes,complement-fixingimmunecomplexdeposition,andinflammatorymediatorsPathologicalFactorsinRheuma7InflammatoryParametersESRAcutephasereactantsImmunoglobulinsComplementcomponentsInflammatorymediators:cytokines,prostanoidsInflammatoryParametersESR8

ESRaredeterminedbythethreeforcesSurfacefreeenergy(VandeWaal＇sforce):cohesiveforceElectricalchargeassociatedwithRBC:repulsiveforceDielectricconstantofthemedium:dissipatestheforceESRaredeterminedbythet9CalculationEquationforESR

Vs=2/9x(Ps-PL)R2/nxgVs=thelimitingvelocityofthesphereR=theradiusofthespherePsandPL=thedensitiesofthesphereandoftheliquidg=theaccelerationduetogravityn=theviscosityoftheliquidCalculationEquationforESR10SerumProteinsandDrugsThatAffecttheESRRateESRincreaseESRdecrease

Fibrinogen

ACTH

Immunoglobulins

Cortisone

Dextran

Ethambutol

Methyldopa

Quinine

Procainamide

Salicylate

Oralcontraceptives

Penicillamine

Methylsergide

Theophylline

Trifluperidol

VitamineASerumProteinsandDrugsThat11AcutePhaseReactantsTheAcutePhaseResponseFollowsCellInjuryandTissueDamageCausedby:Acuteinfections:i.e.,bacterialorparasiticTrauma:i.e.,blunt,surgery,andburnsIschemicnecrosis:i.e.,acutemyocardialinfarctionMalignantdisease:I.e.,tumorgrowthandmetastasisConnectivetissuedisease:i.e.,rheumatoidarthritis,rheumaticfeverandothersAcuteabdominalinflammation:i.e.cholecystitisandpancreatitisVaccination:I.e.,typhoidAcutePhaseReactantsTheAcute12FunctionalPropertiesofHumanAcutePhaseProteinsFunctionalGroupProteinFunctionHostdefenseproteinsC-reactiveprotein(CRP)Complementactivation,opsonicationMannan-bindingprotein(MBP)Complementactivation,opsonizationComplementproteinsC3,C4,C5FactorB,C9FactorH,C4bpIncreasedvascularpermeability,opsonization,bacterialkillingFibrinogenFormationofhemostaticplugs,woundhealingProteinaseinhibitors

1-Proteinaseinhibitor(1-PI)Controlofextracellularmatrixdegradation

1-Antichymotrypsin(1-Achy)Controlofextracellularmatrixdegradation

2-Antiplasmin(2-AP)ControlofplasminC1inhibitor(C1INH)ControlofcomplementandcontacesystemactivationAntioxidantsCeruloplaasminInhibitionofoxyradicalformationHemopexin(Hx)Bindingofheme,inhibitionoflipidperoxidationHaptoglobulin(HP)Bindingofhemoglobulin,inhibitionoflipidperoxidationFunctionunknownSerumamyloidA(SAA)

1-AcidglycoproteinFunctionalPropertiesofHuman13C-ReactiveProtein(CRP)Normalplasmaprotein,concentrationfrom0.068--8.8mg/mlAcutephasereactant,concentrationupto500mg/mlSynthesizedbyhepatocytesMolecularweight105,500daltonsFiveidenticalnon-glycosylated,non-covalentlyassociatedsubunitsAminoacidsequencehomologouswithserumamyloidAcomponent(SAA)C-ReactiveProtein(CRP)Normal14RheumaticDiseaseinWhichElevatedC-ReactiveProteinLevelsmayOccurGoutRheumatoidarthritisJuvenilerheumatoidarthritisPsoriaticarthritisAnkylosingspondylitisReiter＇ssyndromePolymyalgiarheumatica-giantcellarteritisSystemicvasculitisWegener＇sgranulomatosisBehcet＇ssyndromeSystemiclupuserythematosusRheumaticDiseaseinWhichEle15cACR類風(fēng)濕性關(guān)節(jié)炎(RA)cACR類風(fēng)濕性關(guān)節(jié)炎(RA)16類風(fēng)濕性關(guān)節(jié)炎(RA)類風(fēng)濕性關(guān)節(jié)炎是一種重要的自體免疫疾病，可導(dǎo)致關(guān)節(jié)破壞變形，骨骼變化以及全身性的病變。類風(fēng)濕性關(guān)節(jié)炎的骨骼變化包括發(fā)炎關(guān)節(jié)旁的骨缺乏，軟骨侵蝕。類風(fēng)濕性關(guān)節(jié)炎是一種全身性的變化，患者不但關(guān)節(jié)疼痛，可能關(guān)節(jié)會逐漸變形。過去十年來，類風(fēng)濕關(guān)節(jié)炎在冶療上的改變有著明顯的進步。我們不再視其為一僅局限于關(guān)節(jié)的慢性病變；反之，卻視為一甚富侵略性的全身性疾患。類風(fēng)濕性關(guān)節(jié)炎(RA)類風(fēng)濕性關(guān)節(jié)炎是一種重要的自體免疫疾病17RheumatoidArthritis(RA)Achronic,systemic,autoimmune,inflammatorydiseaseofunknownetiologyCharacterizedbypersistentintenseimmunologicalactivityinflammatoryanderosivesynovitis,usuallyinvolvingperipheraljointinasymmetricfashionlocaldestructionofboneandcartilageavarietyofsystemicmanifestation.ThemostcommoninflammatoryjointdiseaseRheumatoidArthritis(RA)18自體免疫疾病課件19NormalSynoviumRheumatoidSynoviumcACRcArthritis&RheumatismFoundationPageNo.20/52NormalSynoviumRheumatoidSyno20自體免疫疾病課件21ClinicalfeaturesofRheumatoidArthritisinthehandEarlyWastingsmallmusclesExtensortendonsheathswellingFusiformswellingofPIPjointsMCPjointsynovitiswithswellingLateDeformityUlnardeviationSwan-neckdeformitySubluxationofMCPJ2.LossoffunctionClinicalfeaturesofRheumatoi22類風(fēng)濕性關(guān)節(jié)炎(RA)類風(fēng)濕性關(guān)節(jié)炎(RA)23RheumatoidarthritisRheumatoidarthritis24類風(fēng)濕性關(guān)節(jié)炎(RA)類風(fēng)濕性關(guān)節(jié)炎(RA)25類風(fēng)濕性關(guān)節(jié)炎(RA)類風(fēng)濕性關(guān)節(jié)炎(RA)26自體免疫疾病課件27類風(fēng)濕關(guān)節(jié)炎的早期關(guān)節(jié)破壞類風(fēng)濕關(guān)節(jié)炎的早期關(guān)節(jié)破壞28類風(fēng)濕性關(guān)節(jié)炎的臨床病程變異性極大只有小于1/5的病人在發(fā)病10-12年內(nèi)沒有出現(xiàn)關(guān)節(jié)破壞或變形在發(fā)病頭六年內(nèi)關(guān)節(jié)破壞進展最快(1st>2nd>3rd..)在發(fā)病頭兩年內(nèi)對于關(guān)節(jié)功能的影響最顯著類風(fēng)濕性關(guān)節(jié)炎的臨床病程變異性極大29MarkersofseverediseaseactivityinRA1.Generalpolyarthritisinvolvingbothsmallandlarge joints2.Extra-articulardisease,especiallynodulesandvasculitis3.PersistentlyelevatedESRorCRPwithactivesynovitis4.RF-positivewithhightitier5.Radiologicallyerosionswithintwoyearsofdiseaseonset6.HLA-DR4positiveMarkersofseverediseaseacti30Majorextra-articularfeaturesofRACommonAnemiaLymphadenopathyRheumatoidnodulesMusclewastingEpiscleritisandkeratoconjuntivitisPeripheralsensorypolyneuropathyUncommonPleuraleffusionPulmonaryfibrosisPericardialeffusionSystemicvasculitisSplenomegalyMajorextra-articularfeatures31RheumatoidFactorsAnautoantibodyreactivewithdenaturedhumanorrabbitIgGGenerationofRFsinthefollowingconditions:Autoimmunedisorders:RA,SLE,Sjogren＇ssyndrome,vasculitisChronicinflammationChronicinfectionMalignancyagingRheumatoidFactorsAnautoantib32SomeDiseaseCommonlyAssociatedwithRheumatoidFactorRheumaticDiseases

Filariasis

RheumatoidarthritisChronicBacterialinfections

Systemiclupuserythematosus

Tuberculosis

Scleroderma

Leprosy

Mixedconnectivetissuedisease

Yaws

Sjogren＇ssyndrome

SyphilisViralInfections

Brucellosis

Acquiredimmunodeficiencysyndromes

Subacutebacterialendocarditis

Mononucleosis

salmonellosis

HepatitisNeoplasms

Influenza

Tumorsafterradiationtherapyorchemotherapy

Aftervaccination(mayyieldfalselyelevatedOtherHyperglobulinemicStates

titersofantivivalantibodies)

HypergammaglobulinemicpurpuraParasiticInfections

Cryoglobulinemia

Trypanosomiasis

Chronicliverdisease

Kala-azar

Sarcoid

Malaria

Otherchronicpulmonarydiseases

SchistosomiasisSomeDiseaseCommonlyAssociat33FalsePositiveRheumatoidFactorTestSarcoidosis10%Syphilis10%Hepatitis25%Viralinfection15%Leprosy25%Subacutebacterialendocarditis50%Oldage(>65y/o)35%FalsePositiveRheumatoidFact34BiomarkersinRheumatoidArthritisRheumatoidfactorAnti-CCP(anti-cycliccitrullinatedpeptides)AbThepresenceofanti-CCPAbisthemostaccuratebiomarkerforRAinbothselectedandunselectedcohortsBiomarkersinRheumatoidArthr35GoalsofRAManagementPainreliefandinflammationreductionActivitiesofdailylivingandqualityoflifeLongtermjointdamagecontrolorpreventionDiseaseprocessinterruptionormodificationTherapyrelatedsideeffectsavoidanceGoalsofRAManagementPainrel36僵直性脊椎關(guān)節(jié)炎(AS)僵直性脊椎關(guān)節(jié)炎(AS)37自體免疫疾病課件38全身紅斑性狼瘡好發(fā)于20-40歲之年輕女性女性與男性之比例約為10:1侵犯多個器官系統(tǒng)?臨床表現(xiàn)千變?nèi)f化難以捉摸全身紅斑性狼瘡好發(fā)于20-40歲之年輕女性39全身紅斑性狼瘡全身紅斑性狼瘡40全身紅斑性狼瘡全身紅斑性狼瘡41全身紅斑性狼瘡與自體抗體患者體內(nèi)常出現(xiàn)許多自體抗體最常出現(xiàn)之自體抗體為抗核抗體(ANA)自體抗體為造成導(dǎo)致器官傷害的重要原因有些自體抗體為追蹤病情之重要指針全身紅斑性狼瘡與自體抗體患者體內(nèi)常出現(xiàn)許多自體抗體42自體免疫疾病課件43自體免疫疾病課件44AntinuclearAntibody(ANA)DiseaseDiseasePatientswithANAs(%)Systemiclupuserythematosus99Drug-inducedlupus100Systemicsclerosis97Mixedconnectivetissuedisease93Polymyositisanddermatomyositis78Sjogren＇ssyndrome96AntinuclearAntibody(ANA)Dis45SpecificAutoantibodiesOrganspecificautoantibodiesAutoantibodiesforsystemicautoimmunedisoedersAutoantibodiesinsystemiclupuserythematosusSpecificAutoantibodiesOrgans46器官特異性自體免疫疾病對應(yīng)抗原的種類疾病自體抗原橋本氏甲狀腺炎(Hashimoto＇sthyroiditis)Thyroidperoxidase(microsomalantigen)ThyroglobulinThyroid-stimulatingimmunoglobulin葛雷氏病(Grave＇sdisease)ThyroidperoxidaseThyroglobulinThyroid-stimulatingimmunoglobulin(TSI)Thyroidgrowth-stimulatingikmmunoglobulin(TGSI)Thyrotropinbinding-inhibitoryimmunoglobulin(TBII)第一型糖尿病Insulin,insulinreceptors,isletcells胰島素抗性糖尿病Insulin,insulinreceptors愛迪生病(Addison＇sdisease)Adrenalcortex惡性貧血(Perniciousanemia)Intrinsicfactor,parietalcells重癥肌無力Acetycholinereceptors多發(fā)性硬化癥(Multiplesclerosis)MyelinbasicproteinGoodpasture＇s病Basementmembrane(lungandglomeruli)尋常性天皰瘡(pemphigusvulgaris)Intracellularcement水泡性類天皰瘡(Bullouspemphigoid)Basementmembrane(skin)非分節(jié)性白斑癥(Non-segmentalvitiligo)Membraneproteinsonkeratinocyteandmelanocyte器官特異性自體免疫疾病對應(yīng)抗原的種類疾47自體免疫抗體與全身性自體免疫疾病之相關(guān)自體免疫抗體相關(guān)之疾病Anti-dsDNASLEAnti-SmSLEAnti-laminSLEAnti-histoneSLE,Drug-inducedlupusAnti-U1RNPSLE,MCTDAnti-SSA/RoSLE,Sjogren＇ssyndromeAnti-SSB/LaSLE,Sjogren＇ssyndromeAnti-PCNA/cyclinSLEAnti-ribosomalPNP-SLEAnti-Scl-70/topoisomeraseISclerodermaAnti-KuSLE,sclerodermaAnti-centromere/kinetochoreCRESTAnti-RNApolymeraseISclerodermaAnti-PM-SclSclerodermaAnti-Jo-1(tRNAsynthetase)PolymyositisAnti-cardiolipinAnti-phospholipidsydnromeAnti-neutrophilcytoplasmicantigenWegener＇sgranulomatosis,othervasculitis自體免疫抗體與全身性自體免疫疾病之相關(guān)自體免疫抗體相關(guān)之疾病48ListofAutoantibodiesReportedinSLEAgainst:1.ANA17.PCNA/Cyclin33.Ribosomal-P47.Poly(ADPribose)2.SsDNA18.HTLV-134.Canephriticfactor,48.Poly(A)polymerase3.DsDNA19.HIV-gp120

C3convertaseC1q49.ProteinkinaseNII4.Z-DNA20.Mycobacteria35.Antiendothelial50.Prothymosin5.PolyI21.Laminin36.Fibronectin51.ReplicationproteinA6.PolyG22.Heatshockprotein(90kD)37.Golgiapparatus52.Sp1007.Poly(dt)23.Klebsiella38.Mitoticspindleapparatus53.RA-338.Histones24.Vimentin39.Mi/Ma/Mc54.Nucleosomes9.Cardiolipin25.Heparansulfate40.AnnexinXI55.Ubiquitine10.ENA26.LAC/FacII,VIII,XII)41.DNApolymerase,56.Glycosaminoglycans11.RNP/hnRNP27.Lymphocytes(LCTA,Ts,NK)

-RNApolymeraseI-III57.Lipocortin-112.Sm28.Erythrocytes(Coombs＇)42.HMG-1,2,1758.Pyruvatedehydrogenase13.SS-A/Ro29.Platelets43.L759.Anti-Pribosomalprotein14.SS-B/La30.Leukocytes44.Nuclearhelicase15.RNA31.Neuronal45.Nucleosides16.Ku/Ki(SL)32.Glycolipids46.C-mycListofAutoantibodiesReporte49全身紅斑性狼瘡常見慢性并發(fā)癥1.腎炎及腎臟衰竭2.中樞神經(jīng)病變3.感染癥4.貧血及血小板降低全身紅斑性狼瘡常見慢性并發(fā)癥1.腎炎及腎臟衰竭2.中樞50自體免疫疾病課件51全身紅斑性狼瘡的活動性與復(fù)發(fā)活動性(SLEactivity)